Biotinylated iodo-polylysine for pretargeted radiation delivery.

Efforts to achieve rapid specific targeting of radioisotopes to disease processes using antibodies conjugated with avidin or streptavidin for pretargeting and radiobiotin derivatives for isotope delivery are attracting substantial interest. At present, these approaches appear to be limited by low delivery of radiotracer to the target. As an alternate radiobiotin tracer, biotinylated/iodinated polylysine (BIP) was prepared by conjugating poly-L-lysine (MW approximately 10,200) with biotin succinimide esters and the Bolton-Hunter reagent. This reagent was then radioiodinated with 125I via the lodogen method. BIP was characterized by radio-HPLC and its in vitro binding to streptavidin. The in vivo localization of BIP was evaluated in a rat model in which streptavidin agarose beads were physically localized to precapillary arterioles in the lungs. Biodistribution and blocking studies performed at 4 and 24 hr after BIP injection indicated specific binding and localization of the radiolabeled peptide to the lungs (lung-to-blood ratio approximately 8 at 4 hr postinjection). Comparative studies of BIP and 111In chelated to biotin showed BIP to have two-fold higher lung targeting and lower splenic and hepatic uptake than the 111In biotin derivative. Our study demonstrates: (1) the feasibility of using a small peptide as a biotin carrier for pretargeting (and for solubilizing organic tracers which may otherwise be difficult to administer in vivo) and (2) that BIP and BIP-like compounds may be suitable and simple alternatives to radiometal-labeled biotin for pretargeting and may offer improved targeting to prelocalized streptavidin.